US7939562B2ExpiredUtilityA1
Amphiphilic derivatives for the production of vesicles, micelles and complexants, and precursors thereof
Est. expiryJan 16, 2021(expired)· nominal 20-yr term from priority
C07C 69/675A61K 9/1075A61K 8/922C07D 213/53C07C 235/28A61K 9/1272A61Q 19/00A61K 8/14A61K 9/0014C07D 303/48C07D 303/04A61K 8/41C07C 69/732A61K 8/416C07C 229/12C07C 301/00A61K 8/4926C07F 9/65505A61K 8/42C07D 407/12C07C 247/12A61K 47/18C07C 229/22A61K 8/46A61K 47/24
60
PatentIndex Score
4
Cited by
26
References
46
Claims
Abstract
Amphiphilic derivatives composed of at least one fatty acid chain are derived from natural vegetable oils such as vernonia oil, lesquerella oil and castor oil, in which the several reactive groups such as epoxy, hydroxy and double bonds can be modified to polar and ionic groups. The head group of the amphiphilic derivative may be in the main fatty acid chain or in a side chain. The amphiphiles are useful for the formation of vesicles and micelles and for use as complexants and surfactants.
Claims
exact text as granted — not AI-modified1. An amphiphilic derivative or a precursor thereof, of the general Formula I:
A 1 -CO—R 1 —R 2 —R 3 —R 4 —R 5 (I)
wherein
R 1 is C 5 -C 10 alkylene;
R 2 is 2,3-oxiranylene, —CH═CH—(CH 2 ) n —, —CH 2 —CH(X)—, —CH(X)—CH(X)—, —(CH═CH—CH(X)) m —, —(CH 2 —CH(X)—CH 2 ) o —, or —(CH(X)—CH(X)—CH 2 ) p —, wherein X is halogen, hydroxy, amino, —O—CO—(CH 2 ) n —R 26 , or —N + (R 22 R 23 R 24 ), n is an integer from 0 to 7, and m, o, and p are integers from 1 to 3;
R 3 is C 1 -C 4 alkylene, optionally substituted by halogen, amino or hydroxy;
R 4 is 2,3-oxiranylene, —CH(OH)—CH(R 25 )—, —CH 2 —CH(R 25 )—, —CH(OH)—CH(X)—, and —CH(OH)—CH(O—CO—R 6 —R 7 —R 8 —R 9 —R 10 )—, wherein X is as defined above in R 2 ;
R 5 is C 1 -C 11 alkyl, and wherein the total sum of carbon atoms in the R 1 —R 2 —R 3 —R4—R 5 chain is at most 23;
A 1 is —NH—R 0 , —O—R 0 , —S—R 0 , or —O—PO(OH) —O—R 0 ;
R 0 is C 1 -C 6 alkyl, or a residue selected from the groups (a)-(h) below, wherein A 1 can only be —O—R 0 when R 0 is C 1 -C 6 alkyl or one of the groups (f), (g), or (h):
(a) —R 11 -Q 1 —CO—R 6 —R 7 —R 8 —R 9 —R 10 ;
(b) —R 17 -Q 1 —CO—R 12 —R 13 —R 14 —R 15 —R 16 ;
(c) —R 19 -Q 1 —R 18 ;
(d) —R 19 -Q 1 —R 20 —G;
(e) —CH 2 —CH(OR 21 )—CH 2 —OR 21 ;
R 6 is C 2 -C 10 alkylene;
R 7 is a covalent bond or as defined for R 2 above;
R 8 is a covalent bond or C 1 -C 4 alkylene;
R 9 is a covalent bond, C 1 -C 14 alkylene, or as defined for R 4 above;
R 10 is C 1 -C 11 alkyl;
Q 1 is a covalent bond, —NH—, —O—, —S—, or —O—PO(OH)—O;
R 11 is a spacer group selected from: C 1 -C 6 alkylene, C 6 -C 14 arylene, —(C 6 -C 14 arylene)—R 28 —(C 6 -C 14 arylene)—, —(CH 2 —CH 2 —O) n —CH 2 —CH 2 —, —(CH 2 —CH 2 —NH) m —CH 2 —CH 2 —, —(CH 2 —CH 2 —S) o —CH 2 —CH 2 —, —(CH(CH 3 )—CH 2 ) p —, —CH(CH 3 )—(CH 2 ) q —CH(CH 3 )—, and —CH 2 —CH(CH 2 —O—R 21 )—, wherein the C 6 -C 14 arylene groups may be substituted each by R 27 , and n, m, o, p and q are integers from 1 to 6;
R 12 is as defined for R 6 above;
R 13 is as defined for R 7 above;
R 14 is as defined for R 8 above;
R 15 is as defined for R 9 above;
R 16 is as defined for R 10 above;
R 17 is as defined for R 11 above or is a group —(CH 2 ) n —N + R 22 R 23 —(CH 2 ) m — or —(CH 2 ) O —NR 22 —(CH 2 ) p —, wherein n, m, o and p are integers from 1 to 4;
G is hydrogen, or a molecule selected from the group consisting of a protein, a polypeptide, an antibody, a polynucleotide, a DNA or a DNA fragment, RNA or RNA fragment, a polysaccharide, a plasmid, and a chemotherapeutic agent;
R 18 is hydrogen; —NR 22 R 23 ; —N + R 22 R 23 R 24 ; —N═CH—(C 6 -C 14 arylene)—N + R 22 R 23 R 24 ; C 1 -C 8 alkyl [optionally substituted by C 6 —C 14 aryl or by R 29 ]; C 6 -C 14 aryl; C 4 -C 9 heteroaryl containing one or more heteroatoms selected from N, O, and S, said C 6 -C 14 aryl and C 4 -C 9 heteroaryl being optionally substituted by C 1 -C 6 alkyl, —(CH 2 ) n —NH 2 , —COOH, —SH, —SO 3 H, —O—SO 2 H, or —O—PO(OH) 2 ; —(CH 2 ) m—(C 6 -C 14 arylene) —R 29 ; —(CH 2 ) O —(C 6 -C 14 arylene)—(CH 2 ) p —R 29 ; —O—PO(OH) —O—CH 2 —CH 2 —N (CH 3 ) 3 + ; —O—PO(OH) —O—CH 2 —CH 2 —NH 2 ; or —O—PO(OH) —O—CH 2 —CH(COO − ) —NH 3 + ; wherein n is an integer from 1 to 6, m and o are integers from 1 to 20, and p is an integer from 0 to 20;
R 19 is as defined for R 11 above, or is a spacer group selected from —CH 2 —(C 6 -C 14 arylene) —R 28 —(C 6 -C 14 arylene) —; bi (C 6 -C 14 ) arylene; bi (C 4 -C 9 ) heteroarylene; and C 4 -C 9 heteroarylene, wherein said bi(C 4 -C 9 )heteroarylene and C 4 -C 9 heteroarylene each contain one or more heteroatoms selected from N, O, and S, and are optionally substituted by —OH, —COOH, —SH, —SO 3 H, —O—SO 2 H, and —O—PO(OH) 2 ;
R 20 is C 1 -C 8 alkylene, optionally substituted by C 6 -C 14 aryl or R 29 ; C 6 -C 14 arylene; or C 4 -C 9 heteroarylene containing one or more heteroatoms selected from N, O, and S, said C 6 -C 14 arylene and C 4 -C 9 heteroarylene being optionally substituted by C 1 -C 6 alkyl, —(CH 2 ) n —NH 2 , —COOH, —SH, —SO 3 H, —O—SO 2 H, or —O—PO(OH) 2 ;
R 21 is —O—PO(OH) 2 , —O—PO(OH) —O—CH 2 —CH 2 —X, wherein X is as defined for R 2 , or —O—PO(OH)—O—CH 2 —CH(COO − )—NH 3 + ;
R 22 , R 23 , and R 24 , independently of each other, are each hydrogen; C 1 -C 20 alkyl or C 6 -C 14 aryl, said C 1 -C 20 alkyl and C 6 -C 14 aryl being optionally substituted by halogen, C 6 -C 14 aryl, —OH, —NH 2 —, —SH, —COOH, —SO 3 H, —O—SO 2 H, —O—PO(OH) 2 , —O—PO(OH)—O—(CH 2 ) 2 —NH 3 + , or —O—PO(OH) —O—CH 2 —CH(COO − )—NH 3 + ; or R 24 is absent and R 22 and R 23 together with the N atom to which they are attached form an aromatic or non-aromatic heterocyclic ring optionally charged in the N atom, said heterocyclic ring optionally containing a further heteroatom selected from N, O, and S, and further being optionally substituted by —NH 2 , —COOH, —CH═N—OH, —OH, —SO 3 H, and —O—PO(OH) 2 ;
R 25 is N 3 ; —O—CO—(C 2 -C 6 alkenyl), —O—CO—(CH 2 ) n —R 26 ; —(CH 2 ) m —O—SO 2 H; —O—SO 2 H; —(CH 2 ) o —COOH; —(CH 2 ) p —O—PO(OH) 2 ; —O—PO(OH) 2 ; —O—PO(OH) —O—(CH 2 ) q —N + R 22 R 23 R 24 ; —N + R 22 R 23 R 24 ; —NR 22 R 23 ; —N + (CH 3 ) 2 —R 30 ; —SR 31 ; —R 32 —(C 6 -C 14 arylene) —R 26 ; or —R 32 —(C 6 -C 14 arylene)—(CH 2 ) r —R 26 , wherein n, m, o, p, and q are integers from 1 to 14, and r is an integer from 1 to 3;
R 26 is halogen; —NR 22 R 23 ; —N + R 22 R 23 R 24 ; —COOH; —SO 3 H; —O—PO(OH) 2 ; —NH—(CH 2 ) n —SO 3 H; —NH—(CH 2 ) m —COOH; —NH—(CH 2 ) o —O—PO(OH) 2 ; —O—PO(OH) —NH—PO(OH) —O—; —N + (CH 3 ) 2 —R 30 ; —O—PO(OH) —O—(CH 2 ) 2 —N + R 22 R 23 R 24 ; —O—PO(OH) —O—(CH 2 ) 2 —NH 3 + ; and —O—PO(OH) —O—CH 2 —CH(COO − )—NH 3 + ; wherein n, m, and o are integers from 1 to 3;
R 27 is —(CH 2 ) n —NR 22 R 23 —, —NH—(CH 2 ) m —SO 3 H, —NH—(CH 2 ) o —COOH, —NH—(CH 2 ) p —O—PO(OH) 2 , —NH—PO(OH) 2 , —NH—(CH 3 ) 2 —R 30 , —NH—(CH 2 ) n —O—PO(OH) —O—(CH 2 ) 2 —NH 3 + , or —NH—(CH 2 ) q —O—PO(OH)—O—CH 2 —CH(COO − )—NH 3 + , wherein n, m, o, p, and q are integers from 0 to 3;
R 28 is C 2 -C 4 alkylene, —C(CH 3 ) 2 —, —O—, —NH—, —S—, or —SO 2 ;
R 29 is —COOH, —NR 22 R 23 , —(CH 2 ) n —N + R 22 R 23 R 24 —, wherein n is an integer from 0 to 3; and as defined for R 27 above;
R 30 is —CH 2 —CH═CH 2 , —CO—CH═CH 2 , —CO—C (CH 3 )═CH 2 , —(CH 2 ) n —N + R 22 R 23 R 24 , —(CH 2 ) m —NH—(CH 2 ) o —SO 3 H, —(CH 2 ) p —NH—(CH 2 ) q —COOH, —(CH 2 ) r —NH—(CH 2 ) s —O—PO(OH) 2 , —PO(OH) 2 , or —O—PO(OH)—O—(CH 2 ) 2 —N + R 22 R 23 R 24 , wherein n, m, p, q, r, and s are integers from 0 to 3;
R 31 is hydrogen, C 2 -C 6 alkenyl with a terminal double bond, —CO—CH═CH 2 , or —CO—C (CH 3 )═CH—NR 22 R 23 ;
R 32 is —NH—, —O—, —S—, —CH 2 —NH—, —CH 2 —S—, or —CH 2 —O—; and salts thereof,
with the proviso that the compounds vernolic acid, trivernolin, N,N′-ethylene bis (vernolamide), N,N′-propylene bis (vernolamide), and 1,2-bis (2-aminoethoxy)ethane N,N′ bis (vernolamide), are excluded, and
wherein R 2 and/or R 4 is substituted by at least one polar, ionic and/or epoxy group and/or by at least one moiety containing at least one polar, ionic and/or epoxy group, said at least one polar, ionic and/or epoxy group and at least one moiety containing at least one polar, ionic and/or epoxy group being substitutions in any combination of 1-2, 1-2-3, 1-2-3-4, 1-2-4-5, 1-2-3-4-5, 1-2-4, 1-2-5, 1-3-4, 1-3, 1-5, 1-4, or 1-2-6 positions of the chain, the position 1 being arbitrarily assigned to the substitution most remote from the CO group, provided that at least one of said polar or ionic group is a polar or ionic head group.
2. An amphiphilic derivative or a precursor thereof according to claim 1 , of the formula Ia:
R 0 —O—CO—R 1 —R 2 —R 3 —R 4 —R 5 (Ia)
wherein
R 1 is C 5 -C 10 alkylene;
R 2 is —CH═CH—(CH 2 ) n —, —CH 2 —CH(X) —, —CH(X) —CH(X) —, —(CH═CH—CH(X)) m —, —(CH 2 —CH(X)—CH 2 ) o —, or —(CH(X)—CH(X)—CH 2 ) p —, wherein X is halogen, amino, or —N 30 (R 22 R 23 R 24 ), n is an integer from 0 to 7, and m, o, and p are integers from 1 to 3;
R 3 is C 2 -C 4 alkylene, optionally substituted by halogen, amino or hydroxy;
R 4 is 2,3-oxiranylene, —CH(OH)—CH(R 25 )—, —CH 2 —CH(R 25 )—, —CH(OH) —CH(X) —, or —CH(OH)—CH(O—CO—R 6 —R 7 —R 8 —R 9 —R 10 )—, wherein X is as defined above in R 2 ;
R 5 is C 1 -C 11 alkyl, wherein the total sum of carbon atoms in the R 2 —R 2 —R 2 —R 4 —R 5 chain is at most 23;
R 0 is C 1 -C 6 alkyl or one of the groups (f), (g), or (h) as defined in claim 1 ; and
wherein R 6 , R 7 , R 8 , R 9 , R 10 , R 22 , R 23 , R 24 and R 25 are as defined in claim 1 .
3. An amphiphilic derivative or a precursor thereof according to claim 2 of the formula Ib:
wherein R 0 , R 1 , R 2 , R 3 , R 5 , and R 25 are as defined in claim 2 .
4. An amphiphilic derivative according to claim 3 herein designated Derivative 1 of the formula:
5. An amphiphilic derivative according to claim 3 of formula Ib, wherein R 25 is —O—CO—(CH 2 ) n —R 26 , wherein n is an integer from 1 to 14, and R 0 , R 1 , R 2 , R 3 , R 5 and R 26 are as defined in claim 3 .
6. An amphiphilic derivative according to claim 1 of the formula Ic:
wherein
R 2 is —CH═CH—(CH 2 ) n — or —CH 2 —CH(X)—, wherein X is hydrogen, halogen, or amino, and n is an integer from 0 to 7;
R 3 is —CH 2 — or —CH(Br)—; and
R 26 is halogen; —NR 22 R 23 ; —N + R 22 R 23 R 24 ; —COOH; —SO 3 H; —O—PO(OH) 2 ; —NH—(CH 2 ) n —SO 3 H; —NH—(CH 2 ) m —COOH; —NH—(CH 2 ) o —O—PO(OH) 2 ; —O—PO(OH)—NH—PO(OH)—O—; —N + (CH 3 ) 2 —R 30 ; —O—PO(OH)—O—(CH 2 ) 2 —N + R 22 R 23 R 24 ; —O—PO(OH) —O—(CH 2 ) 2 —NH 3 + ; and —O—PO(OH) —O—CH 2 —CH(COO − )—NH 3 + ; wherein n, m, and o are integers from 1 to 3; and wherein R 22 , R 23 , R 24 , and R 30 are as defined in claim 1 .
7. An amphiphilic derivative according to claim 6 herein designated Derivative 2, 3, 4, 5 and 28:
wherein X − is a counter ion Cl − , Br − , or I − .
8. An amphiphilic derivative or a precursor thereof according to claim 1 of the formula Id:
R 10 —R 9 —R 8 —R 7 —R 6 —CO—Q 1 —R 11—Q 1 ′ —CO—R 1 —R 2 —R 3 —R 4 —R 5 (Id)
wherein
Q 1 and Q 1 ′, the same or different, represent —NH—, —O—, —S— or —O—PO(OH)—O—; R 11 is the spacer group C 1 -C 6 alkylene or —(CH 2 —CH 2 —NH) m —CH 2 —CH 2 —; R 4 and R 9 , the same or different, are each 2,3-oxiranylene or —CH(OH)—CH(R 25 )—, wherein m is an integer from 1 to 6, and R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 10 , and R 25 are as defined in claim 1 .
9. An amphiphilic derivative according to claim 8 , wherein Q 1 and Q 1 ′ are —O— and R 25 is —N + R 22 R 23 R 24 or —NR 22 R 23 .
10. An amphiphilic derivative according to claim 9 herein designated Derivative 8 and Derivative 9 of the formulas:
11. An amphiphilic derivative according to claim 8 , wherein Q 1 and Q 1 ′ are —NH—, and R 25 is —O—SO 2 H.
12. An amphiphilic derivative according to claim 11 herein designated Derivative 11 of the formula:
13. An amphiphilic derivative according to claim 8 , wherein Q 1 and Q 1 ′ are —NH—; R 4 is —CH(OH)—CH(R 25 )—, and R 9 is —CH(OH)—CH(R′ 25 )—, wherein R 25 and R′ 25 , the same or different, are each —O—CO—(CH 2 ) n —R 26 , wherein R 26 is halogen; —NR 22 R; —N + R 22 R 23 R 24 ; —COOH; —SO 3 H; —O—PO(OH) 2 ;
—NH—(CH 2 ), n —SO 3 H; —NH—(CH 2 ) m —COOH; —NH—(CH 2 ) o —O—PO(OH) 2 ; —O—PO(OH)—NH—PO(OH)—O—; —N + (CH 3 ) 2 —R 30 ; —O—PO(OH)—O—(CH 2 ) 2 —N + R 22 R 23 R 24 ; —O—PO(OH)—O—(CH 2 ) 2 —NH 3 + ; and —O—PO(OH)—O—CH 2 —CH(COO − )—NH 3 + ; and wherein n, m, and o are integers from 1 to 3.
14. An amphiphilic derivative according to claim 13 of the formula Ie:
wherein n is an integer from 1 to 6, and R′ 26 and R″ 26 , the same or different, are each as defined for R 26 .
15. An amphiphilic derivative according to claim 14 herein designated Derivative 7, 10, and 12:
16. An amphiphilic derivative according to claim 8 of the formula Id, wherein R 4 and R 9 are each 2,3-oxiranylene and R 11 is —(CH 2 —CH 2 —NH) m —CH 2 —CH 2 —, wherein m is an integer from 1 to 6.
17. An amphiphilic derivative according to claim 16 herein designated Derivative 15:
18. An amphiphilic derivative according to claim 1 of the formula If:
R 16 —R 15 —R 14 —R 13 —R 12 —CO-Q 1 -R 17 -Q 1 ′-CO—R 1 —R 2 —R 3 —R 4 —R 5 (If)
wherein
Q 1 and Q 1 ′, the same or different, represent —NH—, —O—, —S—, or —O—PO(OH)—O—;
R 17 is —(CH 2 ) n —N + R 22 R 23 —(CH 2 ) m —or (CH 2 ) o —NR 22 —(CH 2 ) p —, wherein n, m, o and p are integers from 1 to 4; C 1 -C 6 alkylene, C 6 -C 24 arylene, —(C 6 -C 14 arylene)—R 28 —(C 6 -C 14 arylene)—(CH 2 —CH 2 —O) n —CH 2 —CH 2 —, —(CH 2 —CH 2 —NH) m —CH 2 —CH 2 —, —(CH 2 —CH 2 —S) o —CH 2 —CH 2 —, —(CH(CH 3 )—CH 2 ) p —, —CH(CH 3 )—(CH 2 ) q —CH(CH 3 )—, and —CH 2 —CH(CH 2 —O—R 21 )—, wherein the C 6 -C 14 arylene groups may be substituted each by R 27 , and n, m, o, p and q are integers from 1 to 6;
R 4 and R 15 independently of each other are 2,3-oxiranylene or —CH(OH)—CH(R 25 )—;
and R 1 , R 2 , R 3 , R 5 , R 6 , R 12 , R 13 , R 14 , R 16 , R 21 , R 22 , R 23 , R 25 and R 28 are as defined in claim 1 .
19. An amphiphilic derivative according to claim 18 of the formula Ig:
wherein W is —N + R 22 R 23 or —NR 22 , n and m are integers from 1 to 4; and R 4 and R 15 are each 2,3-oxiranylene or —CH(OH)—CH(R 25 )—.
20. An amphiphilic derivative according to claim 19 herein designated Derivative 13 and 14:
21. An amphiphilic derivative according to claim 1 of the formula Ih:
R 18 -Q 1 -R 19 -Q 1 ′-CO—R 1 —R 2 —R 3 —R 4 —R 5 (Ih)
wherein
Q 1 represents a covalent bond, —NH—, —O—, —S—, or —O—PO(OH)—O—;
Q 1 ′ represents —NH—, —S—, or —O—PO(OH)—O—;
R 4 is 2,3-oxiranylene or —CH(OH)—CH(R 25 )—;
R 18 is hydrogen, —NR 22 R 23 , —N + R 22 R 23 R 24 , —N═CH—(C 6 -C 14 arylene)—N + R 22 R 23 R 24 , C 1 -C 8 alkyl, optionally substituted by C 6 -C 14 aryl or R 29 ; C 6 -C 24 aryl; C 4 -C 9 heteroaryl containing one or more heteroatoms selected from N, O, and S, said C 6 -C 14 aryl and C 4 -C 9 heteroaryl being optionally substituted by C 1 -C 6 alkyl, —(CH 2 ) n ,—NH 2 , —COOH, —SH, —SO 3 H, —O—SO 2 H, or —O—PO(OH) 2 ; —(CH 2 ) m —(C 6 -C 14 arylene)-R 29 , —(CH 2 ) o —(C 6 -C 14 arylene)-(CH 2 ) p —R 29 , —O—PO(OH)—O—CH 2 —CH 2 —N(CH 3 ) 3 + , —O—PO(OH) —O—CH 2 —CH 2 —NH 2 , or —O—PO(OH)—O—CH 2 —CH(COO − ) —NH 3 + ; wherein n is an integer from 1 to 6, m and o are integers from 1 to 20, and p is an integer from 0 to 20;
R 19 is C 2 -C 6 alkylene, —CH 2 —(C 6 -C 14 arylene)-R 28 —(C 6 -C 14 arylene)-;
and R 2 , R 2 , R 3 , R 5 , R 22 , R 23 , R 24 , R 25 , and R 29 are as defined in claim 1 .
22. An amphiphilic derivative according to claim 21 , wherein R 4 is 2,3-oxiranylene or —CH(OH)—CH(R 25 )—, R 18 is hydrogen, and R 19 is C 1 -C 6 alkylene.
23. An amphiphilic derivative according to claim 22 herein designated Derivative 16, 17, 18, 19 and Derivative 6:
wherein X− is a counterion Cl − , Br − or I − .
24. An amphiphilic derivative according to claim 21 , wherein
Q 1 ′ is —NH—; Q 1 is a covalent bond; R 4 is 2,3-oxiranylene or —CH(OH)—CH(R 25 )—; and
R 18 is hydrogen, —NR 22 R 23 , —N + R 22 R 23 R 24 , or —N═C—(C 6 -C 14 Arylene)-N + R 22 R 23 R 24 ; R 19 is C 1 -C 6 alkylene or —CH 2 —(C 6 -C 14 arylene)-R 28 —(C 6 -C 14 arylene)-.
25. An amphiphilic derivative according to claim 24 herein designated Derivative 20 and 21:
26. An amphiphilic derivative according to claim 1 of the formula Ii:
G-R 20 -Q 1 -R 19 -Q 1 ′-CO—R 1 —R 2 —R 3 —R 4 —R 5 (Ii)
wherein
Q 1 and Q 1 ′, the same or different, represent a covalent bond, —NH—, —O—, —S—, or —O—PO(OH)—O—;
R 4 is 2,3-oxiranylene or —CH(OH)—CH(R 25 )—;
R 19 is C 1 -C 6 alkylene, —CH 2 —(C 6 -C 14 arylene) -R 28 -(C 6 C 14 arylene)-;
R 20 is C 1 - C 8 alkylene, optionally substituted by C 6 -C 14 aryl or R 29 ; C 6 -C 14 arylene; or C 4 -C 9 heteroarylene containing one or more heteroatom selected from N, O, and S, said C 6 -C 14 arylene and C 4 -C 9 heteroarylene being optionally substituted by C 1 -C 6 alkyl, —(CH 2 ) n , —NH 2 , —COOH, —SH, —SO 3 H, —O—SO 2 H, or —O—PO(OH) 2 ;
G is hydrogen, or a residue of a protein, a polypeptide, an antibody, a polynucleotide, a DNA or a DNA fragment, RNA or RNA fragment, a polysaccharide, a plasmid, and or of a chemotherapeutic agent;
and R 1 , R 2 , R 3 , R 5 , R 24 , R 28 , and R 29 are as defined in claim 1 .
27. An amphiphilic derivative according to claim 1 of the formula Ij:
wherein R 21 is hydrogen, —O—PO(OH) 2 , —O—PO(OH)—O—CH 2 —CH 2 —X, , or —O—PO(OH)—O—CH 2 —CH(COO − )—NH 3 + ; and R 1 , R 2 , R 3 , R 4 , R 5 and X are as defined in claim 1 .
28. An amphiphilic derivative according to claim 1 of the formula Ik:
wherein R 21 is hydrogen, —O—PO(OH) 2 , —O—PO(OH)—O—CH 2 —CH 2 —X, or —O—PO(OH)—O—CH 2 —CH(COO − )—NH 3 + ; and R 1 , R 2 , R 3 , R 4 , R 5 and X are as defined in claim 1 .
29. An amphiphilic derivative according to claim 28 , wherein R 2 is —CH═CH—, R 4 is 2,3-oxiranylene, and R 21 is —O—PO(OH) 2 , —O—PO(OH)—O—CH 2 —CH 2 —X, , or —O—PO(OH)—O—CH 2 —CH(COO − )—NH 3 + .
30. An amphiphilic derivative according to claim 29 herein designated Derivative 22 of the formula:
31. An amphiphilic derivative according to claim 1 of the formula Il:
wherein R 21 is hydrogen, —O—PO(OH) 2 , —O—PO(OH)—O—CH 2 —CH 2 —X, or —O—PO(OH)—O—CH 2 —CH(COO − )—NH 3 + ; and R 1 , R 2 , R 3 , R 4 , R 5 and X are as defined in claim 1 .
32. An amphiphilic derivative according to claim 1 of the formula Im:
wherein
R 1 is C 5 -C 20 alkylene;
R 2 is 2,3-oxiranylene, —CH═CH—(CH 2 )n—, —CH 2 —CH(X)—, —CH(X)—CH(X′)—, —(CH═CH—CH(X)) m —, —(CH 2 —CH(X)—CH 2 ) o —, or —(CH(X)—CH(X′)—CH 2 ) p —, wherein X and X′, same or different, are hydrogen, halogen, hydroxy, amino, —O—CO—(CH 2 ) n , —R 26 , or —N + (R 22 R 23 R 24 ), n is an integer from 0 to 7, and m, o, and p are integers from 1 to 3;
R 3 is C 1 -C 4 alkylene, optionally substituted by halogen, amino or hydroxy;
R 4 is 2,3-oxiranylene, —CH(OH)—CH(R 25 )—, —CH 2 —CH(R 25 )—, —CH(OH)—CH(X)—, and —CH(OH)—CH(O—CO—R 6 —R 7 —R 8 —R 9 —R 10 )—;
R 5 is C 1 -C 11 alkyl, and wherein the total sum of carbon atoms in the R 1 —R 2 —R 3 —R 4 —R 5 chain is at most 23;
X is hydrogen, halogen, hydroxy, amino, or —N + (R 22 R 23 R 24 );
and wherein R 6 , R 7 , R 8 , R 9 , R 10 , R 25 , and R 26 are as defined in claim 1 .
33. An amphiphilic derivative according to claim 32 , wherein R 4 or R 2 is —CH(OH)—CH(R 25 )—; R 25 is N 3 , —O—CO—(C 2 -C 6 alkenyl), —O—CO—(CH 2 ) n —R 26 , —(CH 2 ) m —SO 3 H, —O—SO 2 H, —SO 3 H, —(CH 2 ) o —COOH, —(CH 2 ) p —O—PO(OH) 2 , —O—PO(OH) 2 , —O—PO(OH)—O—(CH 2 ) q —N + R 22 R 23 R 24 , —N + R 22 R 23 R 24 , —NR 22 R 23 , —N + (CH 3 ) 2 —R 30 , —SR 31 , —R 32 —(C 6 -C 24 arylene)—R 26 , or —R 32 —(C 6 -C 24 arylene)—(CH 2 ) r —R 26 , wherein n, m, o, p, and q are integers from 1 to 14, and r is an integer from 1 to 3.
34. An amphiphilic derivative according to claim 33 herein designated Derivative 23 of the formula:
wherein X − is a counter ion Cl − , Br − , or I − .
35. An amphiphilic derivative according to claim 33 herein designated Derivative 24 of the formula:
wherein X − is a counter ion Cl − , Br − , or I − .
36. An amphiphilic derivative according to claim 33 herein designated Derivative 25 of the formula:
wherein X − is a counter ion Cl − , Br − , or I − .
37. An amphiphilic derivative according to claim 33 herein designated Derivative 26 of the formula:
38. An amphiphilic derivative according to claim 33 herein designated Derivative 27 of the formula:
39. An amphiphilic derivative according to claim 33 herein designated Derivative 30 of the formula:
40. A precursor of an amphiphilic derivative according to claim 1 herein designated Precursor 1 and 2:
41. A precursor according to claim 8 herein designated Precursor 3:
42. A precursor of an amphiphilic derivative according to claim 14 herein designated Precursor 8 when n=4, Precursor 9 when n=6, and Precursor 10 of the formula:
43. A precursor of an amphiphilic derivative according to claim 15 herein designated Precursor 5 when n=2, and Precursor 7 when n=3of the formula:
44. A precursor of an amphiphilic derivative according to claim 1 herein designated Precursor 12, 13, 14, 15, 16, 17, and 18 of the formulas:
45. Vesicles, micelles, complexants and surfactants made from an amphiphilic derivative according to claim 1 .
46. An amphiphilic derivative according to claim 1 or a precursor thereof, of the general Formula I:
A 1 -CO—R 1 —R 2 —R 3 —R 4 —R 5 (I)
wherein
A 1 is —O—R 0 ;
R 0 is methyl;
R 1 is C 7 alkylene;
R 2 is —CH═CH—;
R 3 is methylene;
R 4 is —CH(OH)—CH(R 25 );
R 5 is C 5 alkyl;
R 25 is —O—CO—(CH 2 ), —R 26 , wherein n is 1;
R 26 is —N + R 22 R 23 R 24 ;
R 22 and R 23 each is methyl; and
R 24 is C 12 H 25 .Cited by (0)
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